Fluoroquinolones May Increase Aortic Aneurysm Risk

Doubling of relative risk observed

Action Points

Use of fluoroquinolones was associated with about a two-fold increase in risk of aortic aneurysm and dissection within 60 days of exposure, according to analysis of a Taiwanese database.

Past use and any prior-year use of fluoroquinolones were similarly associated with an increased, although attenuated, risk.

Both current and past use of fluoroquinolone antibiotics may be associated with an increased risk for life-threatening aortic aneurysm and aortic dissection, researchers reported.

Adults who had recently taken a fluoroquinolone had a roughly two-fold adjusted increased risk for aortic aneurysm or dissection hospitalization in the nested, case-control analysis of data from the Taiwan National Health Insurance Research Database (NHIRD).

Use 2 months to a year prior to hospitalization and prior-year use of one of the broad spectrum antibiotics also appeared to be associated with an increased risk for the severe aortic events, although the risk was attenuated, researcher Chien-Chang Lee, MD, of National Taiwan University Hospital, Douliou, Taiwan, and colleagues wrote in JAMA Internal Medicine.

"We found that use of fluoroquinolones was associated with an approximately 2-fold increase in risk of aortic aneurysm and dissection within 60 days of exposure," the researchers wrote. "Although our results cannot establish cause and effect, it is not likely that more detailed information on a larger population at relatively high-risk of aortic aneurysm or dissection will be available in the immediate future."

The researchers concluded that in the absence of definitive data clinicians should remain, "vigilant for the appearance of aortic aneurysm and dissection in high-risk patients treated with fluoroquinolones."

15,000 Aortic Aneurysm Deaths in U.S. Each Year

The incidence of aortic dissection and aortic aneurysm in the U.S. has risen over the last several decades, with an estimated 15,000 Americans dying each year from aortic aneurysm alone, the researchers wrote.

They noted that patients with congenital disorders associated with defects in the connective tissue protein collagen, such as Marfan syndrome or vascular Ehlers-Danlos syndrome, have been shown to have a higher than normal risk for aneurysm-related dilation and dissection.

Use of fluoroquinolones has also been associated with several collagen-related disorders, including Achilles tendon rupture, tendinopathy, and retinal detachment. In 2008, the FDA announced that it would require a boxed warning about the risk of tendinitis and tendon rupture on fluoroquinolone packaging.

"Not only is tendon composed of collagen, collagen is also a major extracellular matrix component of the aortic wall," the researchers wrote. "As fluoroquinolones may induce degradation of collagen causing tendinopathy, this raises the concern that fluoroquinolones may cause or aggravate aortic aneurysm and dissection by a similar mechanism."

All Users Had Higher Aortic Risk

To test this hypothesis, Lee and colleagues identified 1,477 patients hospitalized for aortic aneurysm or dissection from 2000 through 2011 identified from 1 million NHIRD enrollees. For every case patient, 100 controls matched for age and sex who were not hospitalized for this reason were also included in the study.

The researchers concluded that while these and other major adverse events associated with fluoroquinolone use are uncommon, the increased use of the drugs makes them a significant concern.

"Given the global burden of aortic aneurysm and dissection and the growing use of fluoroquinolones worldwide, well-designed studies in other populations, especially high-risk populations, should be conducted to validate our findings," they wrote, adding that animal studies designed to elucidate the mechanism behind the association would also be useful.

Richard Wunderink, MD, who was not involved with the study, agreed that additional studies are needed. Wunderink is a professor of medicine and pulmonology at Northwestern University Feinberg School of Medicine in Chicago and he is also a spokesman for the American Thoracic Society.

"There are risks and benefits for every drug, and this study may be telling us about another risk for this group of drugs," he told MedPage Today. "Resistance is certainly the biggest issue we face with the quinolones, but these other issues are concerning, even if they are uncommon."

The research was funded by the Taiwan National Science Foundation and the National Taiwan University Hospital.

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